Sulphonylated diphenylethylenediamines, method for their preparation and use in transfer hydrogenation catalysis

ABSTRACT

A diamine of formula (I) is described in which A is hydrogen or a saturated or unsaturated C1-C20 alkyl group or an aryl group; B is a substituted or unsubstituted C1-C20 alkyl, cycloalkyl, alkaryl, alkaryl or aryl group or an alkylamino group and at least one of X 1 , X 2 , Y 1 , Y 2  or Z is a C1-C10 alkyl, cycloalkyl, alkaryl, aralkyl or alkoxy substituting group. The chiral diamine may be used to prepare catalysts suitable for use in transfer hydrogenation reactions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation application claiming priority to U.S. patentapplication Ser. No. 12/493,043 filed Jun. 26, 2009, published as U.S.Patent Publication 2009/0326274 A1, now abandoned, which is acontinuation application claiming priority to U.S. patent applicationSer. No. 11/719,478, filed Jul. 17, 2007, now U.S. Pat. No. 7,667,075,both entitled “Sulphonylated Diphenylethylenediamines, Method for theirPreparation and Use in Transfer Hydrogenation Catalysis.” The parentapplication, U.S. patent application Ser. No. 11/719,478, is a filingunder 35 U.S.C. 371 of International Application No. PCT/GB2005/050190filed Nov. 1, 2005, entitled “Sulphonylated Diphenylethylenediamines,Method for their Preparation and Use in Transfer HydrogenationCatalysis,” claiming priority of United Kingdom Patent Application No.0425320.9 filed Nov. 17, 2004. The above identified patent andapplications are incorporated by reference herein in their entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

REFERENCE TO A MICROFICHE APPENDIX

Not Applicable.

BACKGROUND

This invention relates to diamines and in particular to substituteddiphenylethylenediamines and catalysts derived therefrom. Such catalystsare useful for accelerating asymmetric hydrogenation reactions whoseproducts are useful, for example, as chemical intermediates or reagentsfor use in the production of fine chemicals or pharmaceuticalintermediates.

Catalytic asymmetric hydrogenation involves the activation of molecularhydrogen with chiral metal complexes. However, organic molecules canalso be applied as the hydrogen donor in the presence of a suitablechiral catalyst in a process known as transfer hydrogenation. A hydrogendonor such as isopropanol or formic acid is conventionally used withcatalysts of the type [(sulphonylated diamine)RuCl(arene)] for thereduction of carbonyl groups. This technology provides a powerfulcomplement to catalytic asymmetric hydrogenation. Transferhydrogenation, in fact, is particularly suitable for the asymmetricreduction of ketones that are difficult substrates for hydrogenation,such as acetylenic ketones and cyclic ketones.

Heretofore the sulphonylated diamine component of the transferhydrogenation catalysts has been limited to sulphonylateddiphenylethylenediamine (Dpen) and cycloalkyl-1,2-diamines such as1,2-cyclohexane. For example transfer hydrogenation has been appliedusing [(tosyl-dpen)RuCl(arene)] catalysts to pharmaceutical productssuch as 10-hydroxy-dihydro-dibenz-[b,f]-azepines (see WO 2004/031155).

The sulphonylated diamine components used heretofore, while useful, arenot equally effective across the range of desirable substrates. Thus,there is a need to expand the range of diamines suitable for use intransfer hydrogenation catalysts that provide catalysts of increasedactivity, selectivity or stability. We have recognised that, byintroducing one or more substituting groups into the phenyl rings ofdiphenylethylenediamines and by variation of the sulphonate properties,the steric and electronic properties of the diamine component may beusefully adapted.

SUMMARY

Accordingly the present invention provides a diamine of formula (I)

in which A is hydrogen or a saturated or unsaturated C1-C20 alkyl groupor an aryl group; B is a substituted or unsubstituted C1-C20 alkyl,cycloalkyl, alkaryl, alkaryl or aryl group or an alkylamino group and atleast one of X¹, X², Y¹, Y² or Z is a C1-C10 alkyl, cycloalkyl, alkaryl,aralkyl or alkoxy substituting group.

The invention further provides a method for preparing a diamine offormula (I) comprising the steps of forming a substituted spiroimidazolefrom a substituted. diketone of formula (II), where X¹, X², Y¹, Y² and Zare as above, reducing the substituted spiroimidazole to form asubstituted diamine, optionally resolving the substituted diamine to anenantiomerically enriched form, and sulphonylating the substituteddiamine.

The invention also provides a catalyst comprising the reaction productof a diamine of formula (I) and a suitable compound of a catalyticallyactive metal.

DETAILED DESCRIPTION

In formula (I), A is hydrogen or a saturated or unsaturated C1-C20 alkylgroup or an aryl group. The C1-C20 alkyl groups may be branched orlinear, for example may be methyl, ethyl, n-propyl, iso-propyl, n-butyl,iso-butyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclohexyl,ethyl-hexyl, iso-octyl, n-nonyl, n-decyl, iso-decyl, tridecyl, octadecyland isooctadecyl. The aryl group may be an unsubstituted or substitutedphenyl, naphthyl or anthracylphenyl. Suitable substituting groups arehydroxy, halide (e.g. F, Cl, Br, I), C1-C20 alkoxy, amino, amido,nitrile and thiol. Preferably A is hydrogen, methyl ethyl, propyl orphenyl. Most preferably A is hydrogen.

In formula (I), B is introduced by sulphonylation of the optionallyenantiomerically enriched substituted diamine. A wide range ofsulphonylation compounds may be used to alter the properties of thesulphonylated diamine of formula (I). Accordingly, B may be asubstituted or unsubstituted C1-C20 alkyl, cycloalkyl, alkaryl, alkarylor aryl group, for example as described above, or an alkylamino group.By “alkylamino” we mean that B may be of formula —NR′₂, where R′ is e.g.methyl, cyclohexyl or isopropyl or the nitrogen forms part of an alkylring structure. Fluoroalkyl or fluoroaryl groups may be used, forexample B may be p-CF₃—C₆H₄, C₆F₅ or CF₂CF₂CF₂CF₃ or CF₃. Preferably Bis an aryl group. The aryl group may be an unsubstituted or substitutedphenyl, naphthyl or anthracylphenyl or heteroaryl compound such aspyridyl. Suitable substituting groups are C1-C20 alkyl as describedabove, trifluoromethyl, hydroxyl, halide (e.g. F, Cl, Br, I), C1-C20alkoxy (especially methoxy), amino, amido, nitrile, nitro and thiol.Hence B may be for example o-Nitrophenyl, p-nitrophenyl,trichlorophenyl, trimethoxyphenyl, triisopropylphenyl, o-aminophenyl,benzyl (—CH₂C₆H₅), 2-phenylethyl (C₂H₄C₆H₅), phenyl (C₆H₅), tolyl(p-CH₃—C₆H₄), xylyl ((CH₃)₂C₆H₃), anisyl (CH₃O—C₆H₄), naphthyl or dansyl(5-dimethylamino-1-naphthyl). Preferably, B is tolyl and thesulphonylation is performed with tosyl chloride (p-toluenesulphonylchloride).

The diamine of the present invention has two chiral centres, eachbearing a phenyl ring having at least one substituting group X¹, X², Y¹,Y² or Z. The substituting group X¹, X², Y¹, Y² or Z is a C1-C10 alkyl,cycloalkyl, alkaryl, aralkyl or alkoxy group. It will be understood thatin order to satisfy the valency of the carbon atoms in the phenyl ringsto which X¹, X², Y¹, Y² or Z is bound, where X¹, X², Y¹, Y² or Z is nota C1-C10 alkyl, cycloalkyl, alkaryl, aralkyl or alkoxy substitutinggroup, X¹, X², Y¹, Y² or Z will be a hydrogen atom.

Thus at least one of X¹, X², Y¹, Y² or Z may independently be a C1-C10alkyl group such as methyl, trifluoromethyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl,cyclopentyl, hexyl, cyclohexyl, ethyl-hexyl, iso-octyl, n-nonyl, n-decylor iso-decyl; an alkaryl group such as benzyl or ethylphenyl; an arylgroup such as phenyl, tolyl or xylyl; or a C1-C10 alkoxy group such asmethoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy,sec-butoxy, tert-butoxy, cyclopentoxy, pentoxy, hexoxy, cyclohexoxy,ethyl-hexoxy, iso-octoxy, n-nonoxy, n-decoxy or iso-decoxy.

Preferably each phenyl ring has one or more substituents. The phenylrings may be substituted in one or more positions, i.e. the rings may bemono-, di-, tri-, tetra- or penta-substituted. The substituting group onthe phenyl ring may be in the ortho (X¹, X²), meta (Y¹, Y²) or para (Z)position. However, when the substituent is at the mete-position of thephenyl ring it minimizes the electronic effects on the amino group,which may facilitate the synthesis of the resulting diamine. Thus oneembodiment the substituted diamine is a 1,2-di-(meta-substitutedphenyl)ethylenediamine. Where more that one substituting group ispresent they are preferably the same. For example in one embodiment, Y¹,Y² may be hydrogen and X¹, X² and Z are preferably the same alkyl,cycloalkyl, alkaryl, aralkyl or alkoxy substituting group. In analternative embodiment X¹, X² and Z may be hydrogen and Y¹ and Y² arepreferably the same alkyl, cycloalkyl, alkaryl, aralkyl or alkoxysubstituting group. In a preferred embodiment X¹, X², Y¹ and Y² arehydrogen and Z is a C1-C10 alkyl, cycloalkyl, alkaryl, aralkyl or alkoxysubstituting group. In a particularly preferred embodiment, X¹, X², Y¹and Y² are hydrogen and Z is methyl. In another particularly preferredembodiment, X¹, X², Y¹ and Y² are hydrogen and Z is methoxy.

The substituted diamines of the present invention may be convenientlymade from substituted diketones of formula (II) where X¹, X², Y¹, Y² andZ are as above, via a spiro-imidazole, which is then reduced to adiamine and sulphonylated.

Substituted diketones (benzils) of formula (II) can be obtainedcommercially or can be readily prepared from substituted benzaldehydesof formula (III) where X¹, X², Y¹, Y² and Z are as above, by benzoincondensation followed by oxidation of the resulting substituted benzoin.Substituted benzaldehydes are commercially available or may besynthesised using known substitution reactions. Benzoin condensationreactions are well known and are typically performed by reacting asubstituted benzaldehyde in a suitable solvent in the presence of sodiumcyanide (see for example Ide et al, Org. React. 1948, 4, 269-304). Theoxidation of the substituted benzoin to the diketone may readily beperformed using copper acetate and ammonium nitrate (for example seeWeiss et al, J. Am. Chem. Soc, 1948, 3666).

The spiroimidazole may be formed by treating the substituted diketone offormula (II) with acetic acid, ammonium acetate and cyclohexanone andheating to reflux. The reduction of the resulting substituted benzoin tothe substituted diamine may be performed by mixing a solution of thespiroimidazole with lithium wire and liquid ammonia at below −60° C.,treating the mixture with ethanol and ammonium chloride and allowing themixture to warm to room temperature. The substituted diamine issulphonylated to provide the substituted diamines of the presentinvention.

The substituted diamine may then be sulphonylated by treating thesubstituted diamine in a suitable solvent with the desired sulphonylchloride, i.e. Cl—SO₂—B, and a base such as triethylamine.

The nitrogen atoms in the substituted diamine are bonded to chiralcentres and so the substituted diamine is chiral. The diamine may behomochiral, i.e. (R,R) or (S,S), or have one (R) and one (S) centre.Preferably the diamine is homochiral. Whereas the diamine may be used asa racemic mixture, the amine is preferably enantiomerically enriched.The resolution of the chiral substituted diamine may be performed usinga chiral acid or by any other method known to those skilled in the art.Whereas the resolution may be performed on the sulphonylated diamine offormula (I), preferably the resolution is performed on the substituteddiamine before the sulphonylation step. For example, the substituteddiamine may be treated with a chiral carboxylic acid such asditoluoyltartaric acid or dibenzoyltartaric acid in a suitable solvent.The resolved substituted diamine preferably has an enantiomeric excess(ee %)>70%, more preferably >90%.

Hence this route provides an efficient and cost effective method toprepare enantiomerically enriched substituted1,2-diphenylethylenediamines. The route is depicted below for apreferred example where A, X¹, X², Y¹ and Y² are hydrogen, B is e.g.p-CH₃—C₆H₅ and Z is a C1-C10 alkyl, cycloalkyl, alkaryl, aralkyl oralkoxy substituting group;

Catalysts suitable for performing asymmetric transfer hydrogenationreactions may be prepared by reacting the substituted sulphonylateddiamines of the present invention with a suitable compound of acatalytically active metal. The metal compound is preferably a compoundof metals selected from the list consisting of Ru, Rh, Ir, Co, Ni, Fe,Pd or Pt. Preferred compounds are compounds of Ru, Rh and Ir,particularly Ru or Rh. Suitable Ru or Rh compounds are [MX₂(arene)]₂compounds where M=Rh or Ru and X=halogen, more preferably[RuCl₂(arene)]₂. Arene compounds are any suitable aromatic molecule, andinclude benzenes and cyclopentadienes, e.g. benzene,pentamethylcyclopentadiene and para-cymene (4-isopropyltoluene).Particularly suitable metal compounds for preparing hydrogenationcatalysts include [RhCp*Cl₂]₂ (where Cp* is CpMe₅), [RuCl₂(benzene)]₂and [RuCl₂(p-cymene)]₂.

The catalysts may be prepared by simply combining the diamine and themetal compound in a suitable solvent under mild conditions (e.g. 0 to80° C. at about atmospheric pressure). Suitable solvents includehydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons, esters,alcohols, ethers, DMF and the like. If desired, the reaction may beperformed ex-situ and the resulting catalyst isolated, e.g. by removalof the solvent under vacuum. Alternatively, the catalyst may be formedin-situ, i.e. in the presence of the substrate to be hydrogenated andthe hydrogen source, again by combining the metal compound and diaminein the reactants, which may be diluted with a suitable solvent.

The chiral catalysts of the present invention may be applied to transferhydrogenation reactions. Typically, a carbonyl compound or imine,hydrogen source, base and solvent are mixed in the presence of thecatalyst, which may be formed in-situ. Preferred hydrogen sources areisopropanol or formic acid (or formates). The catalysts may be used toreduce a wide variety of carbonyl compounds to the corresponding chiralalcohols and imines to the corresponding chiral amines. The reactionsmay be carried out under typical transfer hydrogenation conditions andin a variety of suitable solvents known to those skilled in the art. Forexample, the reaction may be performed in an ether, ester ordimethylformamide (DMF) at 0-75° C. Water may be present. With formicacid, a base such as triethylamine, DBU or other tertiary amine ispreferably used. With isopropanol, the base is preferably t-BuOK, KOH oriPrOK.

The invention is illustrated by the following examples.

Example 1 Preparation of Diamine Ligands

(I) Spiro-Imidazole Formation (1 to 2)

a) Z=Methyl (CH₃): Acetic acid (70 ml) was added to a flask containingthe commercially available diketone 1a (dimethylbenzil 11.9 g, 50 mmol)and ammonium acetate (27 g, 350 mmol). Cyclohexanone (5.3 ml, 51.5 mmol)was added and the reaction mixture was heated at reflux for 1-4 hours.After cooling to room temperature, the mixture was poured onto water andleft overnight to crystallize. The crystals were collected by filtrationand dried under reduced pressure. Recrystallization was from ethylacetate/hexane and gave 8.22 and 3.32 g of 2a in 2 crops. Total yield11.54 g, 73%.

b) Z=Methoxy (CH₃O): Acetic acid (100 ml) was added to a flaskcontaining the commercially available diketone 1b (dimethoxybenzil, 18.9g, 70 mmol) and ammonium acetate (37.7 g, 490 mmol). Cyclohexanone (7.45ml, 72.1 mmol) was added and the reaction mixture was heated at refluxfor 1-4 hours. After cooling to room temperature, the mixture was pouredonto water and left overnight to crystallize. The crystals werecollected by filtration and dried under reduced pressure. Yield ofimidazole 2b, 19.22 g, 79%. Further purification can be achieved bycrystallisation from ethyl acetate/hexane.

(II) Reduction (2 to 3)

a) Z=Methyl (CH₃): Ammonia gas was slowly condensed into a solution ofthe spiro-imidazole 2a (6.95 g, 22 mmol) in anhydrous THF (50 ml) at−78° C. under argon. Once the volume of the reaction mixture hasapproximately doubled, the gas flow was stopped. Lithium wire (0.62 g,88 mmol) was added slowly ensuring that the temperature did not exceed−60° C. After stirring for 30-60 minutes ethanol (2.6 ml) was added, and30-60 minutes later ammonium chloride (6.2 g) was added. The mixture wasallowed to warm to room temperature and water (about 100 ml) and MTBE(about 100 ml) were added. The layers were separated and the aqueouslayer was extracted twice with about 100 ml MTBE. The combined organiclayers were washed with brine and evaporated under vacuum. The resultingoil was dissolved in MTBE and 10% HCl was added (2-3 eq.). The biphasicmixture was stirred for 30-90 minutes and was diluted with water. Thelayers were separated and the organic layer was extracted with water.The combined aqueous layers were washed with dichloromethane and thenneutralised with aqueous KOH until the pH>10. The crude diamine wasextracted into dichloromethane (3 times). The combined organic extractsdried (Na₂SO₄) and evaporated to give an oil or solid. Yield of racemicdiamine 3a as a 19:1 mixture of diastereoisomers, 4.96 g, 94%. Furtherpurification can be achieved by crystallisation from ethylacetate/hexane.

b) Z=Methoxy (CH₃O): Ammonia gas was slowly condensed into a solution ofthe spiro-imidazole 2b (6.96 g, 20 mmol) in anhydrous TI-IF (40 ml) at−78° C. under argon. Once the volume of the reaction mixture hasapproximately doubled, the gas flow was stopped. Lithium wire (0.56 g,80 mmol) was added slowly ensuring that the temperature did not exceed−60° C. After stirring for 30-60 minutes ethanol (2.4 ml) was added, and30-60 minutes later ammonium chloride (2.8 g) was added. The mixture wasallowed to warm to room temperature and water (about 100 ml) and MTBE(about 100 ml) were added. The layers were separated and the aqueouslayer was extracted twice with about 100 ml MTBE. The combined organiclayers were washed with brine and evaporated under vacuum. The resultingoil was dissolved in MTBE and 10% HCl was added (2-3 eq.). The biphasicmixture was stirred for 30-90 minutes and was diluted with water. Thelayers were separated and the organic layer was extracted with water.The combined aqueous layers were washed with dichloromethane and thenneutralised with aqueous KOH until the pH>10. The crude diamine wasextracted into dichloromethane (3 times). The combined organic extractsdried (Na₂SO₄) and evaporated to give an oil or solid. Yield of racemicdiamine 3b as a 19:1 mixture of diastereoisomers, 4.69 g, 86%. Furtherpurification can be achieved by crystallisation from ethylacetate/hexane.

(III) Chiral Resolution of Diamines

a) Resolution of diamine 3a. Formation of a salt with ditoluoyltartaricacid in methanol and crystallisation from methanol initially gave (R,R)4a in 94% ee. This can be increased to >99% with one furthercrystallisation.

b) Resolution of diamine 3b. Formation of a salt with ditoluoyltartaricacid in methanol and crystallisation from methanol initially gave (S,S)4b in 74% ee. It should be possible to increase the ee by furthercrystallisation. Formation of a salt with dibenzoyltartaric acid inmethanol and crystallisation from methanol initially gave 4b in 98% ee.

(IV) Synthesis of Mono-Sulfonylated Diamines

a) Tosyl-5a (Z=CH₃, B=4-CH₃—C₆H₄). Triethylamine (210 μl, 1.5 mmol) wasadded to a solution of the diamine 4a (180 mg, 0.75 mmol) in anhydrousdichloromethane (8 ml) and the solution was cooled to 0° C. A solutionof the tosyl chloride (p-toluenesulphonyl chloride, 148 mg, 0.77 mmol)in anhydrous dichloromethane (4 ml) was added slowly. The mixture wasstirred at 0° C. for 30-120 minutes and allowed to warm to roomtemperature over 1-24 hours. Water was added and the layers separated.The aqueous layer was extracted twice with dichloromethane and thecombined organic layers were washed with brine, dried (Na₂SO₄) andevaporated. The crude mono-sulfonated diamine could be purified bycolumn chromatography. Purification by column chromatography gave 270 mg(91%) of Ts-5a as a white solid.

b) Tosyl-5b (Z=OCH₃, B=4-CH₃—C₆H₄). Triethylamine (190 μl, 1.3 mmol) wasadded to a solution of the diamine 4b (175 mg, 0.65 mmol) in anhydrousdichloromethane (8 ml) and the solution was cooled to 0° C. A solutionof the tosyl chloride (p-toluenesulphonyl chloride, 1428 mg, 0.67 mmol)in anhydrous dichloromethane (5 ml) was added slowly. The mixture wasstirred at 0° C. for 30-120 minutes and allowed to warm to roomtemperature over 1-24 hours. Water was added and the layers separated.The aqueous layer was extracted twice with dichloromethane and thecombined organic layers were washed with brine, dried (Na₂SO₄) andevaporated. The crude mono-sulfonylated diamine could be purified bycolumn chromatography. Purification by column chromatography gave 270 mg(91%) of Ts-5b as a white solid.

Example 2 Preparation of Transfer Hydrogenation Catalyst

A mixture of [Ru(p-cymene)Cl₂]₂ (0.5 eq.), triethylamine (2 eq.),mono-sulfonated diamine (1 eq.) 5b in anhydrous isopropanol was heatedat 70-90° C. for 1-4 hours under an inert atmosphere. After cooling toroom temperature the solution was concentrated under reduced pressureand the orange solid collected by filtration. The solid was washed withdegassed water and a small amount of methanol then further dried underreduced pressure. Further purification can be performed byprecipitation/crystallisation from hot methanol.

Example 3 Use of Mono-Sulfonated Diamines 5 for Asymmetric TransferHydrogenation Test of Transfer Hydrogenation Catalysts on a Mixture ofKetones

Transfer hydrogenation catalysts bearing diamines 5 were prepared insitu and tested on pre-formed mixture of ketones in DMF.[Ru(p-cymene)Cl₂]₂ (0.0025 mmol) or [RhCp*Cl₂]₂ (0.0025 mmol)mono-sulfonated diamine (0.0055 mmol) 5 in anhydrous DMF (2 mL) wereheated at 40° C. for 10 minutes under inert atmosphere (argon). Asolution of five ketones (0.5 mL, 1 mmol in total, 0.2 mmol each) in DMFwas added (S/C 40 with respect to each substrate), followed by 0.6 mL offormic acid/trietylamine 1/1 mixture and 1 mL of DMF. The reaction washeated overnight (20 hrs) at 60° C. and analysed by CG (ChiraDex CBcolumn, 10 psi He, 100° C. for 12 min, then to 180° C. at 1.5° C./min,then to 200° C. at 5° C./min).

For reference, the diamines tested were as follows:

                Ketone

(S,S)-Ts-DAEN-Ru >95% conv 33% conv >95% conv >95% conv >95% conv S/C100/1   55% ee 40% ee   96% ee   29% ee   92% ee (S,S)-Ts-DAEN-Ru >95%conv 10% conv >95% conv >95% conv >95% conv S/C 200/1   57% ee 42% ee  98% ee   27% ee   94% ee (R,R)-Ts-DTEN-Ru >95% conv 11% conv >95%conv >95% conv >95% conv S/C 200/1   53% ee 35% ee   96% ee   28% ee  91% ee (S,S)-Ts-DAEN-Rh >95% conv 46% conv   51% conv >95% conv   47%conv S/C 100/1   72% ee 13% ee   98% ee   13% ee   90% ee conv =conversion ee enantiomeric excess

The results show particularly high conversions and ee's are obtained forthe cyclic ketone, i.e. where the ketone is part of a ring structure,such as α-tetralone.

Example 4 Activity of TsDAEN vs. TsDPEN

The activity of (S,S)-TsDAEN vs the conventional (S,S)-TsDPEN inasymmetric transfer hydrogenation was tested using α-tetralone as asubstrate. The reaction was performed on a 15 mmol scale, at S/C 500/1,using [RuCl₂(p-cymene)]₂ as metal precursor and DMF as solvent at 60° C.One equivalent of triethylammonium formate was added at the beginning ofthe reaction and more HCOOH was added during the course of the reactionto maintain the pH at 8.2. The results shown below indicate that(S,S)-TsDAEN is more active than (S,S)-TsDPEN.

Diamine Ligand Time (h) Conversion (%) e.e. (%) Example 4 (S,S)-TsDAEN1.5 36 98 5 71 22 90 Comparative (S,S)-TsDPEN 1 11 98 Example 2 25 3 314 36 6 45 22 70

What is claimed is:
 1. A diamine of formula (I)

in which A is hydrogen or a saturated or unsaturated C1-C20 alkyl groupor an aryl group; B is a substituted or unsubstituted C1-C20 alkyl,cycloalkyl, alkaryl, or aryl group or an alkylamino group and either (i)Z is hydrogen and at least one of X¹, X², Y¹ and Y² is a C1-C10 alkyl,cycloalkyl, alkaryl, aralkyl or alkoxy substituting group or (ii) Z is aC1-C10 alkyl, alkaryl, cycloalkyl, aralkyl or alkoxy substituting groupand at least one of X¹, X², Y¹, Y² and Z is a C1-C10 alkyl, alkaryl,cycloalkyl, aralkyl or alkoxy substituting group.
 2. The diamineaccording to claim 1 wherein A is hydrogen.
 3. The diamine according toclaim 1 wherein B is a substituted or unsubstituted aryl group.
 4. Thediamine according to claim 1 wherein Z is hydrogen and at least one ofX¹, X², Y¹ and Y² is a C1-C10 alkyl, alkaryl, cycloalkyl, aralkyl oralkoxy substituting group.
 5. The diamine according to claim 1 wherein Zis a C1-C10 alkyl, alkaryl, cycloalkyl, aralkyl or alkoxy substitutinggroup and at least one of X¹, X², Y¹, Y² and Z are a C1-C10 alkyl,alkaryl, cycloalkyl, aralkyl or alkoxy substituting group.
 6. Thediamine according to claim 5 wherein one of X¹, X², Y¹ and Y² is aC1-C10 alkyl, alkaryl, cycloalkyl, aralkyl or alkoxy substituting group.7. The diamine according to claim 1 wherein the diamine is homochiral.8. The method for preparing a diamine of formula (I) as claimed in claim1 comprising the steps of a) forming a substituted spiroimidazole from asubstituted diketone of formula (II), b) reducing the substitutedspiroimidazole to form a substituted diamine, c) optionally resolvingthe substituted diamine to an enantiomerically enriched form, and d)sulphonylating the substituted diamine


9. A catalyst comprising the reaction product of a diamine of formula(I) as claimed in claim 1 and a compound of a metal selected from thelist consisting of Ru, Rh, Ir, Co, Ni, Fe, Pd or Pt.
 10. The catalystaccording to claim 9 wherein the metal compound is [MX₂(arene)]₂ whereM=Rh or Ru and X=halogen.
 11. A method comprising contacting thecatalyst according to claim 9 with a compound and performing a transferhydrogenation reaction.
 12. The method according to claim 11 wherein thecompound is a cyclic ketone.
 13. The diamine according to claim 5wherein two of X¹, X², Y¹ and Y² are a C1-C10 alkyl, alkaryl,cycloalkyl, aralkyl or alkoxy substituting group.
 14. The diamineaccording to claim 5 wherein three of X¹, X², Y¹ and Y² are a C1-C10alkyl, alkaryl, cycloalkyl, aralkyl or alkoxy substituting group. 15.The diamine according to claim 5 wherein four of X¹, X², Y¹ and Y² are aC1-C10 alkyl, alkaryl, cycloalkyl, aralkyl or alkoxy substituting group.16. The diamine according to claim 3 wherein B is a substituted phenylgroup.
 17. The diamine according to claim 4 wherein B is 4-methylphenyl,4-methoxyphenyl or 4-chlorophenyl.
 18. The diamine according to claim 5wherein B is 4-methylphenyl.
 19. The diamine according to claim 4wherein B is 1-naphthyl.
 20. The diamine according to claim 1 wherein Bis benzyl.
 21. The diamine according to claim 1 wherein B is methyl. 22.The catalyst according to claim 10 wherein the metal compound is[MCl₂(p-cymene)]_(z).
 23. A method of reducing a compound comprisingcontacting the catalyst according to claim 9 with an unreduced form of a10-hydroxy-dihydro-dibenz-[b,f]-azepine under conditions suitable forperforming a transfer hydrogenation reaction.